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WO2018123135A1 - Dispositif de mesure de substance biologique - Google Patents

Dispositif de mesure de substance biologique Download PDF

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Publication number
WO2018123135A1
WO2018123135A1 PCT/JP2017/030555 JP2017030555W WO2018123135A1 WO 2018123135 A1 WO2018123135 A1 WO 2018123135A1 JP 2017030555 W JP2017030555 W JP 2017030555W WO 2018123135 A1 WO2018123135 A1 WO 2018123135A1
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WO
WIPO (PCT)
Prior art keywords
infrared light
atr prism
face
biological material
contact
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2017/030555
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English (en)
Japanese (ja)
Inventor
新平 小川
大介 藤澤
浩一 秋山
健太郎 榎
弘介 篠原
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Mitsubishi Electric Corp
Original Assignee
Mitsubishi Electric Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Mitsubishi Electric Corp filed Critical Mitsubishi Electric Corp
Priority to DE112017006544.5T priority Critical patent/DE112017006544B4/de
Priority to US16/344,124 priority patent/US11234648B2/en
Priority to CN201780077002.2A priority patent/CN110087542B/zh
Priority to CN202110971379.0A priority patent/CN113662537B/zh
Priority to JP2018558804A priority patent/JP6742439B2/ja
Publication of WO2018123135A1 publication Critical patent/WO2018123135A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6843—Monitoring or controlling sensor contact pressure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0048—Detecting, measuring or recording by applying mechanical forces or stimuli
    • A61B5/0051—Detecting, measuring or recording by applying mechanical forces or stimuli by applying vibrations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0093—Detecting, measuring or recording by applying one single type of energy and measuring its conversion into another type of energy
    • A61B5/0095—Detecting, measuring or recording by applying one single type of energy and measuring its conversion into another type of energy by applying light and detecting acoustic waves, i.e. photoacoustic measurements
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6813—Specially adapted to be attached to a specific body part
    • A61B5/6814—Head
    • A61B5/682—Mouth, e.g., oral cavity; tongue; Lips; Teeth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/02—Details of sensors specially adapted for in-vivo measurements
    • A61B2562/0261—Strain gauges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters

Definitions

  • the present invention relates to a biological material measuring device, and more particularly to a biological material measuring device that measures biological materials such as sugar existing in a living body using infrared light.
  • the SN ratio is improved by measurement using an ATR (Attenuated Total Reflection) prism.
  • ATR Attenuated Total Reflection
  • the infrared light propagating through the ATR prism repeats total reflection at the interface between the skin to be measured and the ATR prism.
  • Evanescent light is generated at the totally reflecting boundary surface and enters the skin to be measured. Since evanescent light is absorbed and scattered by water, sugar, and other biological materials, the intensity of infrared light propagating through the ATR prism is attenuated. Therefore, as the number of times of total reflection is increased, the intensity of propagating infrared light is attenuated.
  • a semiconductor quantum cascade as an infrared light source, it is possible to reduce the size so that it can be mounted on a mobile phone.
  • Patent Document 2 Japanese Patent Application Laid-Open No. 2015-173935
  • a force sensor is installed in the vicinity of the ATR prism in order to confirm the degree of adhesion with the measurement skin.
  • JP 2003-42952 A Japanese Patent Laying-Open No. 2015-173935
  • the skin is composed of the epidermis near the surface and the dermis below the epidermis.
  • the epidermis includes a stratum corneum, a granular layer, a spiny layer, and a basal layer in order from the vicinity of the surface.
  • Sugars and other biological substances are present in tissue interstitial fluid in the epidermis, and are considered to be unevenly distributed in the depth direction reflecting the structure of the epidermis.
  • the epidermis structure is distorted.
  • the contact state between the ATR prism and the skin surface changes, so the contact stress that the skin surface receives from the ATR prism changes, so the distribution of tissue interstitial fluid in the epidermis also changes, and the infrared rays absorbed by sugar and other biological materials Variations occur in the intensity of the light evanescent light.
  • Patent Document 2 a force sensor is installed near the ATR prism to indirectly monitor the presence or absence of a gap, but the contact state between the ATR prism and the skin to be measured cannot always be measured with high accuracy.
  • an object of the present invention is to provide a biological material measuring apparatus capable of measuring the amount of biological material in the measured skin after accurately measuring the contact state between the ATR prism and the measured skin. That is.
  • a biological material measuring apparatus includes an infrared light source that emits infrared light that radiates infrared light in the entire absorption wavelength or a partial wavelength region of the biological material, and red on the first end face. Infrared light emitted from the external light source is incident, the infrared light incident on the second end surface and the third end surface is transmitted through the inside while repeating total reflection, and the infrared light transmitted from the fourth end surface ATR prism that emits light, an infrared light detector that detects infrared light emitted from the ATR prism by separating wavelengths, and a contact state between the ATR prism and the living body surface are detected. And a contact sensor configured to do so.
  • the contact state between the ATR prism and the skin to be measured can be measured with high accuracy by using the contact sensor.
  • FIG. 2 is a diagram illustrating a configuration of a portable non-invasive blood sugar level sensor 80 according to Embodiment 1.
  • FIG. It is a figure which shows the fingerprint spectrum of sugar.
  • FIG. 3 is a diagram illustrating a structure of a head of the non-invasive blood sugar level sensor 80 according to the first embodiment. It is a figure for demonstrating the method to measure the contact state of the to-be-measured skin 49 and ATR prism 20 using distortion sensor 37a, 37b, 37c.
  • 3 is a flowchart illustrating an operation procedure of the non-invasive blood sugar level sensor according to the first embodiment.
  • FIG. 1 It is a figure which shows the structure of the sensor head of the noninvasive blood glucose level sensor of Embodiment 2.
  • FIG. It is a figure for demonstrating the method to measure the contact state of the ATR prism 20 and the to-be-measured skin 49 using the surface acoustic wave generation part 39 and the surface acoustic wave detection part 40.
  • FIG. It is a figure showing the outline of the alternating voltage detected by the detection circuit 62 when contact pressure is P1 and P2.
  • 6 is a diagram illustrating an outline of a non-invasive blood sugar level sensor according to Embodiment 3.
  • FIG. It is the figure which looked at the ATR prism 20 which has a one-dimensional diffraction grating from the contact surface with the to-be-measured skin 49.
  • FIG. 12 is a cross-sectional view taken along the line AA ′ of the ATR prism 20 of FIG. 11.
  • FIG. 5 is a view of the two-dimensional diffraction grating ATR prism 20 as seen from the contact surface with the skin 49 to be measured.
  • FIG. 14 is a cross-sectional view taken along the line BB ′ of the ATR prism 20 of FIG. 6 is a schematic diagram of a sensor array 1000 included in an infrared light detector 30 according to Embodiment 3.
  • FIG. It is a figure showing a mode when the contact state of the ATR prism 20 and the to-be-measured skin 49 is an optimal contact state.
  • FIG. 10 is a diagram illustrating an ATR prism 20 according to a fifth embodiment.
  • FIG. 10 is a diagram illustrating an ATR prism 20 according to a fifth embodiment.
  • FIG. 18 is a top view of the ATR prism 20 of FIG. 17. It is a figure showing the structure of the infrared-light detector 30 of Embodiment 6.
  • FIG. FIG. 10 is a top view of a semiconductor optical device 100 according to a sixth embodiment. 3 is a top view of the semiconductor optical device 100 in which the absorber 10 is omitted.
  • FIG. FIG. 22 is a cross-sectional view (including the absorber 10) when the semiconductor optical device 100 of FIG. 21 is viewed in the III-III direction.
  • 1 is a diagram illustrating an absorber 10 included in a semiconductor optical device 100.
  • Embodiment 1 FIG.
  • the measurement apparatus of the present invention is not limited to the measurement of a blood glucose level, and can be applied to the measurement of other biological substances.
  • FIG. 1 is a diagram illustrating a usage example of a portable non-invasive blood sugar level sensor 80 according to the embodiment.
  • the head of a portable non-invasive blood sugar level sensor 80 is brought into contact with the thin lips of the subject's keratin to measure the blood sugar level in the subject's body.
  • the site to be measured is preferably a thin horny lip, but is not limited to this, and may be any site other than a thick horny region such as a palm. For example, measurements can be made on the face cheeks, ear lobes, and back of the hand.
  • FIG. 2 is a diagram illustrating a configuration of the portable non-invasive blood sugar level sensor 80 according to the first embodiment.
  • the non-invasive blood sugar level sensor 80 includes an ATR prism 20, an infrared light source 32, an infrared light detector 30, a control unit 52, and a user interface 54.
  • the infrared light source 32 emits infrared light in the whole or part of the absorption wavelength of the biological material.
  • the infrared light detector 30 detects the infrared light emitted from the ATR prism 20.
  • the control unit 52 controls the infrared light source 32 and the infrared light detector 30.
  • the controller 52 calculates the concentration of the blood glucose level in the living body based on the intensity of the infrared light detected by the infrared light detector 30.
  • the user interface 54 includes a display 501, a vibrator 502, and a keyboard 503.
  • the ATR prism 20 is mounted on the head of the non-invasive blood sugar level sensor 80.
  • the ATR prism 20 is in contact with the skin 49 to be measured which is the surface of the subject's living body.
  • the non-invasive blood sugar level sensor 80 is activated by bringing the ATR prism 20 into contact with the surface of the subject's living body, the entire wavelength range of 8.5 ⁇ m to 10 ⁇ m including the sugar fingerprint spectrum from the infrared light source 32 is obtained. Infrared light in the wavelength range or a part of the wavelength range is emitted.
  • FIG. 3 is a diagram showing a fingerprint spectrum of sugar.
  • the incident infrared light 11a emitted from the infrared light source 32 is reflected by the end face 20c of the ATR prism 20 and becomes the propagation infrared light 11b.
  • the propagating infrared light 11b passes through the inside of the ATR prism 20 in contact with the skin 49 to be measured while repeating total reflection at the end surfaces 20a and 20b of the ATR prism 20.
  • the propagating infrared light 11b that has passed through the ATR prism 20 is reflected by the end face 20d of the ATR prism 20 and becomes radiant infrared light 11c.
  • the intensity of the radiant infrared light 11 c is detected by the infrared light detector 30.
  • Evanescent light is generated at the interface (end surface 20a) between the ATR prism 20 and the skin 49 to be measured in total reflection. This evanescent light enters the skin 49 to be measured and is absorbed by sugar.
  • the evanescent light becomes large.
  • the evanescent light that oozes out from the ATR prism 20 to the measured skin 49 side when totally reflected at the interface (end surface 20a) is absorbed by the biological material in the measured skin 49, and thus totally reflected by the end surface 20a.
  • the intensity of infrared light is attenuated. Therefore, if the biological material in the skin 49 to be measured is large, the evanescent light is absorbed more, and the intensity of the totally reflected infrared light is greatly attenuated.
  • the skin is composed of the epidermis near the surface and the dermis below the epidermis.
  • the epidermis includes a stratum corneum, a granular layer, a spiny layer, and a basal layer in order from the vicinity of the surface. Each thickness is about 10 ⁇ m, several ⁇ m, 100 ⁇ m, and several ⁇ m. Cells are generated in the basal layer and stacked in the spiny layer. In the granular layer, moisture (tissue interstitial fluid) does not reach and the cells die. In the stratum corneum, dead cells are hardened. Sugars and other biological materials are present in tissue interstitial fluid in the epidermis. Tissue interstitial fluid increases from the stratum corneum to the spinous layer. Therefore, the intensity of the totally reflected infrared light changes according to the penetration length of the evanescent light.
  • the evanescent light attenuates exponentially from the interface toward the skin 49 to be measured, and the penetration length is about the wavelength. Therefore, in the spectroscopy using the ATR prism 20, the amount of the biological material in the region up to the penetration length can be measured. For example, since the sugar fingerprint spectrum has a wavelength of 8.5 ⁇ m to 10 ⁇ m, the amount of sugar in the region of about 8.5 ⁇ m to 10 ⁇ m from the prism surface of the ATR prism 20 can be detected.
  • FIG. 4 is a diagram showing the structure of the head of the non-invasive blood sugar level sensor 80 of the first embodiment.
  • the head includes a substrate 50, an ATR prism 20, an infrared light source 32, an infrared light detector 30, a support base 36, and strain sensors 37a, b, and c.
  • the ATR prism 20 has a shape in which a part of a rectangular parallelepiped is cut off.
  • the cross section of the ATR prism has a shape in which two apex angles of a rectangle are cut at a constant angle. As shown in FIG. 4, the shorter surface whose apex angle is cut is brought into contact with the skin as a measurement surface in contact with the skin 49 to be measured.
  • the angle of the end surface 20 c of the ATR prism 20 is set so that the propagating infrared light 11 b in the ATR prism 20 is totally reflected on the end surfaces 20 a and 20 b of the ATR prism 20. Further, the angle of the end surface 20 d of the ATR prism 20 is set so that the radiated infrared light 11 c is directed toward the infrared light detector 30.
  • the end face 20c where the incident infrared light 11a from the infrared light source 32 is incident and the end face 20d where the radiated infrared light 11c is emitted to the infrared light detector 30 are provided with a non-reflective coating.
  • the incident infrared light 11a from the infrared light source 32 is changed to p-polarized light (polarized light is parallel to the substrate 50), and the incident surface 20c and the output surface 20d are cut so that the incident / exit angle becomes the Brewster angle. It is good also as what has been done.
  • a single crystal of zinc sulfide (ZnS) that is transparent in the mid-infrared region and has a relatively low refractive index is used.
  • the material of the ATR prism 20 is not limited to a single crystal of zinc sulfide (ZnS), and may be a known material such as zinc selenide (ZnSe).
  • the contact surface 20a of the ATR prism 20 with the skin is coated with a thin film such as SiO 2 or SiN so as not to harm the human body.
  • the infrared light source 32 for example, a quantum cascade laser module is used.
  • the quantum cascade laser is a single light source, has a large output, and has a high signal-to-noise ratio (SNR), so that highly accurate measurement is possible.
  • the quantum cascade laser module is equipped with a lens for collimating the beam.
  • the quantum cascade laser emits infrared light in all or part of the wavelength range of 8.5 ⁇ m to 10 ⁇ m where the sugar fingerprint spectrum exists.
  • the infrared light source 32 emits infrared light in the entire wavelength range of 8.5 ⁇ m to 10 ⁇ m or a part of the wavelength range including the wavelength of the sugar fingerprint spectrum.
  • the infrared light detector 30 is a sensor module equipped with a non-cooling sensor such as a MEMS (Micro Electro Mechanical Systems) type sensor or a thermopile.
  • the sensor module includes an electric circuit such as a preamplifier and a lens for condensing light on the sensor element.
  • FIG. 5 is a diagram for explaining a method of measuring the contact state between the skin 49 to be measured and the ATR prism 20 using the strain sensors 37a, 37b, and 37c.
  • the ATR prism 20, the infrared light source 32, the infrared light detector 30, and the support base 36 are disposed on the substrate 50.
  • the support base 36 supports the ATR prism 20.
  • the ATR prism 20 is equipped with strain sensors 37a, 37b, 37c, which are a kind of contact sensors for measuring stress from the contact surface with the skin 49 to be measured.
  • the strain sensors 37a, 37b, and 37c measure the stress between the substrate 50 and the support base 36.
  • the strain sensors 37a, 37b, and 37c are disposed at positions that do not directly contact the skin 49 to be measured.
  • the first surface which is a surface perpendicular to the measurement surface that contacts the skin 49 to be measured, and the substrate 50 are in contact.
  • the second surface that is the surface facing the measurement surface that contacts the skin 49 to be measured and the support base 36 are in contact with each other.
  • the strain sensors 37a and 37b are attached to the second surface, that is, the surface of the ATR prism 20 that contacts the support base 36.
  • the strain sensor 37 c is attached to the first surface, that is, the surface of the ATR prism 20 that contacts the substrate 50.
  • Measurement circuits 38a, 38b, and 38c measure resistance values of the strain sensors 37a, 37b, and 37c.
  • the pressing force can be calculated from the average value of the output values of the strain sensors 37a and 37b.
  • the contact angle in the longitudinal direction of the ATR prism 20 can be calculated from the difference value between the output values of the strain sensors 37a and 37b. Further, by using the output value from the strain sensor 37c in addition to the average value of the output values of the strain sensor 37a and the strain sensor 37b, information on the contact angle in the short direction can be obtained.
  • the strain sensors 37a, 37b, and 37c can be metal thin wires whose resistance changes due to expansion and contraction due to applied force. If the resistance R is changed by ⁇ R when the length L is changed by ⁇ L due to distortion applied to the thin metal wire, the following equation is established.
  • Ks is a coefficient representing the sensitivity of the strain gauge
  • ⁇ is the strain amount. Since ⁇ R is small, a Wheatstone bridge circuit is used.
  • the control unit 52 includes resistors Ra, Rb, Rc of the strain sensors 37a, 37b, 37c sent from the measurement circuits 38a, 38b, 38c, and initial values Ra0, Rb0, Rc0 of the resistors Ra, Rb, Rc (the ATR prism 20 And the initial value of the length of the strain sensors 37a, 37b, 37c (the length when not in contact with the measured skin 49).
  • the lengths ⁇ La, ⁇ Lb, and ⁇ Lc are obtained.
  • the controller 52 calculates the contact stress and the contact angle between the ATR prism 20 and the skin 49 to be measured as described above.
  • the strain sensors 37a, 37b, and 37c are measured with the strain sensors 37a, 37b, and 37c by calculating the contact stress between the ATR prism 20 and the skin 49 to be measured. Measurement is possible without direct contact with the measurement skin 49. As a result, in the present embodiment, the degree of freedom of the contact area between the ATR prism 20 and the skin 49 to be measured is increased, so that the load on the person to be measured for measurement can be reduced. In the present embodiment, since the measurement area is increased, the measurement accuracy is increased.
  • FIG. 6 is a flowchart showing an operation procedure of the noninvasive blood sugar level sensor according to the first embodiment.
  • step S101 the control unit 52 determines whether or not the measurement start is instructed through the keyboard 503. If the user instructs to start measurement, the process proceeds to step S102.
  • step S102 the control unit 52 outputs a message sound from the speaker 504 or vibrates the vibrator 502, thereby transmitting a message prompting the start of contact with the skin to be measured 49 of the ATR prism 20.
  • a message voice such as “please make the sensor tip touch the lips for measurement preparation” is output.
  • the adjustment of the contact portion may be prompted by outputting a message voice such as “Please adjust the sensor tip”.
  • step S103 the control unit 52 starts measuring the contact state between the ATR prism 20 and the skin 49 to be measured.
  • the controller 52 calculates the contact state between the ATR prism 20 and the skin 49 to be measured, that is, the contact stress and the contact angle, based on the resistance values of the strain sensors 37a, 37b, and 37c.
  • step S104 the control unit 52 determines whether or not the measured contact state satisfies a condition that can ensure detection accuracy.
  • the condition can be, for example, within a predetermined range where the contact stress is present or a certain threshold value or more. If the condition is satisfied, the process proceeds to step S105.
  • step S105 the control unit 52 outputs a message sound such as “Adjustment of sensor tip has been completed” from the speaker 504, thereby notifying the user of completion of contact adjustment.
  • step S106 the control unit 52 notifies the user of the start of blood glucose measurement by outputting a message voice such as “Continue to start measurement” from the speaker 504.
  • step S107 the control unit 52 starts measuring the blood sugar level.
  • step S108 the control unit 52 determines whether the measurement of the blood sugar level is completed. If completed, the process proceeds to step S109.
  • step S109 the control unit 52 outputs a message voice such as “Measurement is completed” from the speaker 504.
  • step S110 the control unit 52 calculates a blood glucose level based on the measured intensity of infrared light.
  • step S111 the control unit 52 displays the calculated blood glucose level on the display 501.
  • the contact state between the ATR prism and the skin to be measured can be measured with high accuracy by using the strain sensor attached to the ATR prism.
  • FIG. FIG. 7 is a diagram illustrating a structure of a sensor head of the noninvasive blood sugar level sensor according to the second embodiment.
  • This sensor head includes a substrate 50, an ATR prism 20, an infrared light source 32, an infrared light detector 30, and a surface acoustic wave device which is a kind of contact sensor.
  • the surface acoustic wave device includes a surface acoustic wave generator 39 and a surface acoustic wave detector 40.
  • the substrate 50, the ATR prism 20, the infrared light source 32, and the infrared light detector 30 are the same as those in the first embodiment, description thereof will not be repeated.
  • the ATR prism 20 has the same shape and material as in the first embodiment, and is provided with the same coating.
  • a crystal having no central symmetry such as ZnS or ZnSe constituting the ATR prism 20 exhibits a piezoelectric property and has a property of being distorted when a voltage is applied.
  • FIG. 8 is a diagram for explaining a method of measuring the contact state between the ATR prism 20 and the skin 49 to be measured using the surface acoustic wave generation unit 39 and the surface acoustic wave detection unit 40.
  • the surface acoustic wave generator 39 is configured by a first comb-shaped electrode formed at one end of the measurement surface that contacts the skin 49 to be measured among the plurality of surfaces of the ATR prism 20.
  • the first comb-shaped electrode is connected to the AC voltage power supply 41.
  • the first comb-shaped electrode generates a surface acoustic wave when an AC voltage from the AC voltage power supply 41 is applied.
  • the surface acoustic wave detection unit 40 is configured by a second comb-shaped electrode formed on the other end of the measurement surface that contacts the skin 49 to be measured among the plurality of surfaces of the ATR prism 20.
  • the second comb-shaped electrode is connected to the detection circuit 62.
  • the amplitude or propagation speed of the surface acoustic wave that is output from the surface acoustic wave generator 39 and propagates through the measurement surface of the ATR prism 20 changes.
  • the surface acoustic wave detection unit 40 detects the surface acoustic wave that has propagated through the surface of the ATR prism 20 and outputs an AC voltage corresponding to the amplitude and phase of the surface acoustic wave.
  • the detection circuit 62 detects the amplitude and phase of the AC voltage output from the surface acoustic wave detector 40.
  • the control unit 52 Based on the amplitude and phase of the AC voltage output from the surface acoustic wave detection unit 40, the control unit 52 obtains the amplitude and propagation speed of the surface acoustic wave transmitted through the measurement surface of the ATR prism 20.
  • the control unit 52 obtains the contact stress between the ATR prism 20 and the skin 49 to be measured based on the amplitude and propagation velocity of the surface acoustic wave.
  • FIG. 9 is a diagram showing an outline of the AC voltage detected by the detection circuit 62 when the contact pressure is P1 and P2.
  • P1 ⁇ P2.
  • the amplitude of the alternating voltage at the large contact pressure P2 is smaller than the amplitude of the alternating voltage at the small contact pressure P1. Further, the phase of the AC voltage at the large contact pressure P2 is advanced from the phase of the AC voltage at the small contact pressure P1. Therefore, when the contact pressure increases, the amplitude of the surface acoustic wave propagating through the surface of the ATR prism 20 decreases and the propagation speed increases.
  • the contact state between the ATR prism and the skin to be measured can be measured with high accuracy by using the surface acoustic wave device attached to the ATR prism.
  • FIG. 10 is a diagram schematically illustrating the noninvasive blood sugar level sensor according to the third embodiment.
  • the light emitted from the infrared light source 32 reaches the ATR prism 20, and the incident light that has passed through the ATR prism 20 reaches the infrared light detector 30.
  • the infrared light source 32 outputs light having a wavelength ⁇ 1 that is absorbed by the human sugar and infrared light having a reference wavelength ⁇ 2 that is not absorbed by the human sugar.
  • the wavelengths ⁇ 1 and ⁇ 2 are set to very close values, so that the influence of the infrared rays radiated from the background and the human body becomes almost equal, so that the influence of noise can be minimized.
  • the diffraction grating 18 is provided on the surface of the ATR prism 20 that contacts the skin 49 to be measured.
  • the diffraction grating 18 may be a one-dimensional periodic pattern (hereinafter referred to as a one-dimensional diffraction grating) or a two-dimensional periodic uneven pattern (hereinafter referred to as a two-dimensional diffraction grating). May be.
  • FIG. 11 and 12 are diagrams showing a diffraction grating having a one-dimensional diffraction grating.
  • FIG. 11 is a view of the ATR prism 20 having a one-dimensional diffraction grating as viewed from the contact surface with the skin 49 to be measured.
  • FIG. 12 is a cross-sectional view taken along the line AA ′ of the ATR prism 20 of FIG.
  • FIG. 13 and FIG. 14 are diagrams showing a diffraction grating having a two-dimensional diffraction grating.
  • FIG. 13 is a view of the two-dimensional diffraction grating ATR prism 20 as seen from the contact surface with the skin 49 to be measured.
  • FIG. 14 is a cross-sectional view taken along the line BB ′ of the ATR prism 20 of FIG.
  • a diffraction phenomenon occurs, that is, whether or not to resonate greatly depends on polarization.
  • the interaction between the diffraction grating and the light emitted from the infrared light source 32 (incident light) varies depending on the direction of the groove of the one-dimensional diffraction grating and the direction of the electric field (polarized light). For example, a diffraction phenomenon is more likely to occur when the direction of the groove and the direction of the electric field are orthogonal.
  • the diffraction phenomenon of the two-dimensional diffraction grating largely depends on the polarization as compared with the one-dimensional diffraction grating having the pattern of only the one-dimensional X direction. No, but it depends somewhat on polarization. Therefore, it is possible to easily cause the diffraction phenomenon by providing the incident light with polarization beforehand.
  • the infrared light detector 30 is disposed at a position where the light emitted from the ATR prism 20 at the reflection angles ⁇ 1 and ⁇ 2 can be received vertically.
  • the incident light is diffracted by the diffraction grating 18 on the surface.
  • a metal thin film 60 such as gold is provided on the surface of the diffraction grating 18.
  • surface plasmon resonance of the diffraction grating 18 occurs. If the thickness of the metal thin film 60 and the type of metal are determined, the incident angle of light to the diffraction grating 18 where surface plasmon resonance occurs is determined by the wavelength.
  • the size of the surface plasmon varies depending on the period and depth of the diffraction grating 18 or the size of the unevenness.
  • the surface plasmon can be maximized by adjusting the period and depth of the diffraction grating 18 so that the signal light (wavelengths ⁇ 1 and ⁇ 2) propagates on the surface or produces Wood's anomaly.
  • the surface plasmon is maximized, that is, when the electromagnetic field enhancement is maximized, absorption of evanescent light due to blood glucose at these wavelengths ⁇ 1 and ⁇ 2 is maximized, and blood glucose detection sensitivity can be increased. .
  • the incident angle and wavelength can also be controlled by the periodic structure of the diffraction grating 18.
  • FIG. 15 is a schematic diagram of a sensor array 1000 included in the infrared light detector 30 of the third embodiment.
  • the sensor array 1000 includes uncooled infrared sensors (hereinafter also referred to as sensor pixels) 110 and 120 that detect light having different wavelengths.
  • Each of the sensor pixels 110 and 120 includes, for example, a wavelength selection structure unit 11 using plasmon resonance on the surface of the light receiving unit.
  • the period of the two-dimensional periodic structure of the wavelength selection structure unit 11 is made substantially equal to the wavelength ⁇ 1 or ⁇ 2.
  • infrared light having a selected wavelength ⁇ 1 or ⁇ 2 is detected.
  • the infrared light detector 30 including an array of uncooled infrared sensors that detect only infrared light of the selected wavelength ⁇ 1 or ⁇ 2
  • a plurality of wavelengths can be measured simultaneously, so that measurement in a short time is possible. It becomes possible.
  • the infrared light detector 30 has wavelength selectivity, noise other than the signal light (wavelengths ⁇ 1, ⁇ 2), for example, light emitted from the human body or the environment can be blocked.
  • the sensor pixels 110 and 120 of the infrared light detector 30 detect infrared light having wavelengths of ⁇ 1 and ⁇ 2.
  • Infrared light of wavelength ⁇ 1 is absorbed not only by sugar but also by water and other biological materials
  • infrared light of wavelength ⁇ 2 is not absorbed by sugar and is absorbed by water and other biological materials. Is done.
  • the control unit 52 obtains the absorption amount by the sugar by correcting the detected intensity of the infrared light having the wavelength of ⁇ 1 using the intensity of the infrared light having the wavelength of ⁇ 2. Thereby, measurement accuracy can be improved.
  • the refractive index of the infrared light diffraction grating 18 varies depending on the degree of contact between the ATR prism 20 and the skin 49 to be measured (that is, the magnitude of the contact stress).
  • the reflection angle of light from the diffraction grating 18 changes due to the change in the refractive index. Therefore, the infrared light emission angle is uniquely determined by the degree of adhesion. Therefore, the degree of adhesion can be determined by using the infrared light detector 30.
  • the exit angle from 20 is obtained in advance.
  • the infrared light detector 30 When measuring a biological material, the infrared light detector 30 is rotated around the infrared light emission point of the ATR prism 20.
  • the control unit 52 obtains an emission angle from the ATR prism 20 when the infrared light detector 30 detects infrared light.
  • the control unit 52 obtains the degree of contact (contact stress) of contact between the measured skin 49 and the ATR prism 20 corresponding to the obtained emission angle.
  • the contact stress obtained here is used in step S104 in FIG.
  • the ATR prism 20 and the skin 49 to be measured are brought into close contact with each other by using the diffraction grating 18 and the sensitive wavelength and incident angle dependence characteristics of the infrared light detector 30. Whether or not the blood glucose level can be determined with high accuracy improves blood glucose level measurement accuracy.
  • the infrared light source 32 itself may be pulse-driven at a constant frequency, and the detection sensitivity may be increased by chopping using the frequency.
  • Embodiment 4 By pressing the ATR prism 20 against the skin 49 to be measured, the skin 49 to be measured enters between the diffraction gratings 18, so that the refractive index changes compared to before pressing.
  • the state in which the skin 49 to be measured enters the entire groove portion of the diffraction grating 18 and the diffraction grating 18 and the skin 49 to be measured are in close contact with each other with no gap is defined as an optimum contact state.
  • the optimal contact state the absorption of evanescent light by the sugar is maximized and the intensity of the reflected light is minimized.
  • FIG. 16 is a diagram illustrating a state in which the contact state between the ATR prism 20 and the skin 49 to be measured is the optimal contact state.
  • the refractive index of the infrared light in the optimum contact state is obtained in advance by calculation, and the reflection angle of the light from the diffraction grating 18 is obtained in advance based on the refractive index in the optimum contact state.
  • the infrared light detector 30 receives light emitted from the ATR prism 20 vertically only in the optimum contact state. Even when the contact state is not optimal, infrared light enters the infrared light detector 30, but the output from the infrared light detector 30 cannot be obtained because the incident angle is not vertical as will be described later.
  • the amount of biological material can be measured only when the ATR prism and the skin to be measured are in an optimal contact state.
  • FIG. 17 is a diagram illustrating the ATR prism 20 of the fifth embodiment.
  • FIG. 18 is a top view of the ATR prism 20 of FIG.
  • the metal patch 65 is periodically arranged on the contact surface of the skin 49 to be measured of the ATR prism 20.
  • the metal patch 65 is preferably square, circular, or cross-shaped.
  • the metal patches 65 are two-dimensionally periodically arranged in a square lattice or a triangular lattice.
  • the metal patch 65 is a rectangle or an ellipse, it has an asymmetric shape in a two-dimensional plane, and polarization dependency occurs.
  • the metal patch 65 is a thin film of 50 to 100 nm. When this thickness is sufficiently smaller than the target wavelength, for example, when it is as small as 1/100, diffraction does not occur.
  • plasmon resonance is determined by the size and period of the metal patch 65 and does not depend on the incident angle of infrared light on the ATR prism 20.
  • the surrounding environment greatly affects the plasmon resonance wavelength. That is, the resonance wavelength is determined by the degree of close contact between the skin 49 to be measured and the ATR prism 20.
  • the resonance wavelength is around 10 microns.
  • the resonance wavelength does not depend on the incident angle of the infrared light to the ATR prism 20
  • the accuracy of the angle at which the ATR prism 20 is installed with respect to the infrared light source 32 is not questioned. Therefore, there is an effect of improving accuracy such that the portable device is resistant to vibration.
  • the amount of biological material can be measured only when the ATR prism and the skin to be measured are in an optimal contact state.
  • FIG. 19 is a diagram illustrating the configuration of the infrared light detector 30 according to the sixth embodiment.
  • This infrared light detector 30 is an integrated wavelength selective infrared sensor.
  • the infrared light detector 30 includes a sensor array 1000 and a detection circuit 1010.
  • the sensor array 1000 includes 9 ⁇ 6 pixels (semiconductor optical elements) 100 arranged in a matrix. On the substrate 1, 9 ⁇ 6 semiconductor optical devices 100 are arranged in a matrix (array) in the X-axis and Y-axis directions. Light enters from a direction parallel to the Z axis.
  • the detection circuit 1010 is provided around the sensor array 1000.
  • the detection circuit 1010 detects an image by processing a signal detected by the semiconductor optical device 100.
  • the detection circuit 1010 does not need to detect an image when the detection wavelength is small, and may detect the output from each element.
  • FIG. 20 is a top view of the semiconductor optical device 100.
  • the semiconductor optical device 100 includes an absorber 10.
  • FIG. 21 is a top view of the semiconductor optical device 100 from which the absorber 10 is omitted.
  • the protective film and the reflective film on the wiring are omitted for clarity.
  • 22 is a cross-sectional view (including the absorber 10) when the semiconductor optical device 100 of FIG. 21 is viewed in the III-III direction.
  • FIG. 23 is a diagram illustrating the absorber 10 included in the semiconductor optical device 100.
  • the semiconductor optical device 100 includes a substrate 1 made of silicon, for example.
  • the substrate 1 is provided with a hollow portion 2.
  • a temperature detector 4 for detecting temperature is disposed on the hollow portion 2.
  • the temperature detector 4 is supported by two support legs 3.
  • the support leg 3 has a bridge shape that is bent in an L shape when viewed from above.
  • the support leg 3 includes a thin film metal wiring 6 and a dielectric film 16 that supports the thin film metal wiring 6.
  • the temperature detection unit 4 includes a detection film 5 and a thin film metal wiring 6.
  • the detection film 5 is made of a diode using crystalline silicon, for example.
  • the thin film metal wiring 6 is also provided on the support leg 3 and electrically connects the aluminum wiring 7 covered with the insulating film 12 and the detection film 5.
  • the thin film metal wiring 6 is made of, for example, a titanium alloy having a thickness of 100 nm.
  • the electrical signal output from the detection film 5 is transmitted to the aluminum wiring 7 through the thin film metal wiring 6 formed on the support leg 3, and is taken out by the detection circuit 1010 in FIG. Electrical connection between the thin-film metal wiring 6 and the detection film 5 and between the thin-film metal wiring 6 and the aluminum wiring 7 is performed via a conductor (not shown) extending in the vertical direction as necessary. May be.
  • the reflective film 8 that reflects infrared rays is disposed so as to cover the hollow portion 2.
  • the reflective film 8 and the temperature detection unit 4 are arranged so as to cover at least a part of the support leg 3 in a state where they are not thermally connected.
  • the support pillar 9 is provided above the temperature detection part 4 as shown in FIG.
  • the absorber 10 is supported on the support column 9. That is, the absorber 10 is connected by the temperature detection unit 4 and the support column 9. Since the absorber 10 is thermally connected to the temperature detector 4, the temperature change generated in the absorber 10 is transmitted to the temperature detector 4.
  • the absorber 10 is disposed above the reflective film 8 in a state where it is not thermally connected to the reflective film 8.
  • the absorber 10 spreads in a plate shape on the side so as to cover at least part of the reflective film 8. Therefore, as shown in FIG. 20, the semiconductor optical device 100 can only see the absorber 10 when viewed from above.
  • the absorber 10 may be formed directly on the temperature detection unit 4.
  • the surface of the absorber 10 is provided with a wavelength selection structure 11 that selectively absorbs light having a certain wavelength, as shown in FIG. Further, an absorption preventing film 13 for preventing light absorption from the back surface is provided on the back surface of the absorber 10, that is, on the support pillar 9 side. With this configuration, the absorber 10 can selectively absorb light having a certain wavelength. In addition, since the light absorption may occur also in the wavelength selection structure unit 11, the absorber 10 including the wavelength selection structure unit 11 is used in the present embodiment.
  • the wavelength selection structure unit 11 has a structure using surface plasmons.
  • a metal periodic structure is provided on the light incident surface, surface plasmons are generated at a wavelength corresponding to the surface periodic structure, and light is absorbed. Therefore, the surface of the absorber 10 can be made of metal, and the wavelength selectivity of the absorber 10 can be controlled by the wavelength of incident light, the incident angle, and the periodic structure of the metal surface.
  • the phenomenon contributed by free electrons inside the metal film and the generation of the surface mode by the periodic structure are considered to be synonymous from the viewpoint of absorption, and without distinguishing both, surface plasmon, This is called surface plasmon resonance, or simply resonance.
  • surface plasmon resonance or simply resonance.
  • it may be called a pseudo surface plasmon and a metamaterial, it treats as the same thing from the viewpoint of absorption.
  • the configuration of the present embodiment is also effective in light having a wavelength range other than infrared, for example, wavelengths in the visible, near infrared, and THz regions.
  • the wavelength selection structure 11 that selectively increases the absorption of light having a certain wavelength provided on the surface of the absorber 10 includes a metal film 42, a main body 43, and a recess 45.
  • the type of the metal film 42 provided on the surface of the absorber 10 is selected from metals that easily cause surface plasmon resonance, such as Au, Ag, Cu, Al, Ni, or Mo. Alternatively, any material that causes plasmon resonance such as metal nitride such as TiN, metal boride, and metal carbide may be used.
  • the film thickness of the metal film 42 on the surface of the absorber 10 may be a thickness that does not transmit incident infrared light. With such a film thickness, only surface plasmon resonance on the surface of the absorber 10 affects absorption and emission of electromagnetic waves, and the material under the metal film 42 does not optically affect absorption or the like.
  • the skin effect depth ⁇ 1 is expressed by the following equation.
  • ⁇ 1 (2 / ⁇ ) 1/2
  • the film thickness ⁇ of the metal film 42 on the surface of the absorber 10 is at least twice as large as ⁇ 1, that is, about several tens nm to several hundreds nm, the leakage of incident light to the lower part of the absorber 10 is Can be small enough.
  • the absorber composed of the surfaces of the silicon oxide main body 43 and the gold metal film 42 can have a smaller heat capacity than the absorber composed of only gold, and as a result, the response can be accelerated.
  • a method for producing the absorber 10 will be described. After a periodic structure is formed on the surface side of the main body 43 made of a dielectric or semiconductor using photolithography and dry etching, the metal film 42 is formed by sputtering or the like. Next, similarly, the metal film 42 is formed on the back surface after forming the periodic structure.
  • the diameter of the recess 45 is as small as about several ⁇ m, it is easier to manufacture the metal film 42 after forming the recess by etching the main body 43 than to directly etch the metal film 42 to form the recess. The process becomes easy. Further, since an expensive material such as Au or Ag is used for the metal film 42, the amount of metal used can be reduced by using the dielectric or semiconductor body 43, and the cost can be reduced.
  • the absorption wavelength is about 8 ⁇ m.
  • the relationship between the absorption wavelength and emission wavelength of incident light and the period of the recess 45 is almost the same in the arrangement of a square lattice, a triangular lattice, etc., as long as it is a two-dimensional periodic structure. It is determined by the period of the recess 45. Considering the reciprocal lattice vector of the periodic structure, theoretically, in the square lattice arrangement, the absorption and emission wavelengths are almost equal to the period, whereas in the triangular lattice arrangement, the absorption and emission wavelengths are the period ⁇ ⁇ 3/2. However, since the absorption and emission wavelengths slightly change depending on the diameter d of the concave portion 45 in practice, it is considered that a wavelength substantially equal to the period is absorbed or emitted in either periodic structure.
  • the wavelength of the absorbed infrared light can be controlled by the period of the recess 45.
  • the diameter d of the recess 45 is desirably 1/2 or more of the period p.
  • the resonance effect is reduced, and the absorption rate tends to decrease.
  • the resonance is a three-dimensional resonance in the recess 45, sufficient absorption may be obtained even if the diameter d is smaller than 1 ⁇ 2 of the period p. Therefore, the value of the diameter d with respect to the period p is Designed individually as appropriate. What is important is that the absorption wavelength is mainly controlled by the period p.
  • the absorber 10 has sufficient absorption characteristics, so that the design can be widened.
  • the absorbed light is independent of the depth h of the recess 45 and depends only on the period p. Therefore, the absorption wavelength and the emission wavelength do not depend on the depth h of the recess 45 shown in FIG.
  • the absorption of the absorber 10 having these concavo-convex structures is maximized in the case of normal incidence.
  • the angle of incidence on the absorber 10 deviates from normal incidence, the absorption wavelength also changes and the absorption decreases.
  • a contact sensor for detecting pressure due to contact between the ATR prism 20 and the skin 49 to be measured a capacitance sensor, a semiconductor piezoresistive sensor, a silicon resonant sensor A sensor or the like can also be used.

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Abstract

L'invention concerne une source de lumière infrarouge (32) émettant de la lumière infrarouge. La lumière infrarouge émise par la source de lumière infrarouge (32) entre dans une première face d'extrémité d'un prisme ATR (20). Le prisme ATR (20) permet à la lumière infrarouge entrant par l'intermédiaire d'une deuxième face d'extrémité et d'une troisième face d'extrémité d'être transmise à l'intérieur à travers ces dernières, tout en amenant la lumière infrarouge à être réfléchie spéculairement de façon répétée, et délivre la lumière infrarouge transmise par l'intermédiaire de la troisième face d'extrémité. Un détecteur de lumière infrarouge (30) détecte l'intensité de la lumière infrarouge délivrée par le prisme ATR (20). Un capteur de contrainte (37a), (37b), (37c) en tant que type de capteur de contact est monté sur le prisme ATR (20), et est configuré pour détecter un état de contact entre le prisme ATR (20) et la peau (49) à mesurer.
PCT/JP2017/030555 2016-12-26 2017-08-25 Dispositif de mesure de substance biologique Ceased WO2018123135A1 (fr)

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DE112017006544.5T DE112017006544B4 (de) 2016-12-26 2017-08-25 Messgerät für biologisches material
US16/344,124 US11234648B2 (en) 2016-12-26 2017-08-25 Biological material measuring apparatus
CN201780077002.2A CN110087542B (zh) 2016-12-26 2017-08-25 生物体物质测量装置
CN202110971379.0A CN113662537B (zh) 2016-12-26 2017-08-25 生物体物质测量装置
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